John G Bartlett Johns Hopkins University School of Medicine Conflicts None HIV REVIEW History Current standards Future HIV NATURAL HISTORY HIV transmission ID: 776382
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HIV: HISTORYCURRENT STATUS AND FUTURE
John G. BartlettJohns Hopkins UniversitySchool of Medicine Conflicts -- None
Slide2HIV REVIEW
History
Current standards
Future
Slide3HIV NATURAL HISTORY
HIV transmission ↓ 2- 4 weeksAcute HIV (50 – 90 %) ↓ 1- 3 weeksAsymptomatic ↓ 8 yearsAIDS ↓ 1.3 yearsDeath
Slide4Slide5HIV RISK CATEGORIES (2010)CDC data – 48,298 cases
MSM (gay men) – 63%Injection drug use – 8%Heterosexual transmission – 25% Blood transfusions – 0% Perinatal transmission – (162)African American – 44%Poverty – 2.1% (8 x ↑)
Slide6HIV: HISTORY 1981-2013
1981: PCP Cluster
1994: ACTG 076
1982: “AIDS”named
1996: Vancouver IAS – “HAART”
1983: HIV reported
1997: FDA accepts Viral Load as
end point
1985: Serologic test
2003: PEPFAR born
1986: AZT trial
2008: First cure
1987: Act-up
2012: Prevention and cure
1990: Ryan White Act
2013: “AIDS-free generation” –
Hilary Clinton
1991: Magic Johnson
Slide7CDC: MMWR June 5, 1981
9 MSM with PCP
CDC: MMWR July 3, 1981
Slide8HIV/AIDS – FIRST DECADE
HIV
: Circa 1981-91
Patients
: Most died
Diarrhea
Dementia
Disgrace
Image: IDU & MSM
Fear: Contagion
Untreatable
Slide9WHO WINNING PHOTO AWARD:
AIDS – THE HUMAN TRAGEDY
Slide10ID/IMMUNOLOGY:Wegener disease & polyarteritis nodosa; Director of NIAID
Anthony Fauci“Goose pimples” 1981
Slide111984 Ryan White
Child with hemophilia
– HIV discovered 12/17/84 – banned from school and given 6 month diagnosis. Died 5 years later, 4 months before passage of the Ryan White Care Act – now $2 billion/year for HIV drugs for 500,000. Bono – “Greatest man I ever met”
Slide12C. Everett Koop“The Letter” 1987
Surgeon General under President ReaganChampion of – Sex educationCondomsHandicapped childrenCigarette harm“The Letter” was an AIDS wakeup call
Slide13AIDS QUILT – 1987
Panel are 3’ by 6’ with tributes to people who were lost to HIV → Washington Mall 1987-1996, weight = 54 tons, 94,000 names (20%)
Slide14AIDS COALITION to UNLEASH POWER: 1987
Civil disobedience: Wall Street 1987, NY Post Office 1987, St. Patrick’s Cathedral 1989, NIH 1990 (Now TAG)
Slide15Martin DelaneyActivist (without AIDS)1945-2008
Founded Project Inform “for medically supervised guerrilla trials” – Major force in NIAID, FDA and ethics
Slide16The Trial: AZT vs. placebo (n=282). DSMB stopped study: 19 deaths (placebo) vs. 1 (AZT)(Fischl MA. NEJM 1987;317:185)
Slide17Jeff Murray, MDDeputy DirectorDivision of Antimicrobial Drug Products for FDA
Major facilitator of HIV drugs (n=28) and, more recently HCV (#24 in trials)
Slide18MAGIC JOHNSONThe Announcement: 1991
“I have AIDS”(Trumped efforts of millions to destigmatize HIV infection)
Slide19PROTEASE 1996
The development of protease inhibitors and beginning of HAART
Slide20■
IDV / 3TC / AZT
● IDV∆ AZT / 3TC
THE STUDY THAT CHANGED AIDSGulick RM. Merck 035 NEJM 1997;337:734
HAART: IDV/AZT/3TC
Results for NDV at 52 weeks – 80% vs. zero
Slide21David Ho
“Hit hard and hit early” …Time Magazine: Man-of-the-year, 1996
Slide22Mortality From 1990-2004 in the Johns Hopkins HIV Clinical Cohort
Lau B, et al.
Non-AIDS Related Mortality Risk Exceeds AIDS-related Mortality Among Injecting Drug Users with CD4+ Counts Above 200 Cells/mm3. CROI Denver, CO, 2006
Slide23NRTI NNRTI PI El CCR5 II1987 AZT ------ ------ ------ ------ ------1991-92 ddI, ddC ------ ------ ------ ------ ------1995 d4T ------ ------ ------ ------ ------1996 3TC ------ SQV ------ ------ ------1997 ------ NVP RTV, IDV ------ ------ ------1997 ------ DLV NFV ------ ------ ------1998 ------ EFV ------ ------ ------ ------1999 ABC ------ APV ------ ------ ------2000 ------ ------ LPV ------ ------ ------2001 TDF ------ ------ ------ ------ ------2003 FTC ------ ATV ENF ------ ------2005 ------ ------ TPV ------ ------ ------2006 ------ ------ DRV ------ ------ ------ ------ ------ ------ ------ MVC RAL ------ ETR ------ ------ ------ ------ ------ RPV ------ ------ ------ ------ ------ ------ ------ ------ ------ EVG2013 ------ ------ ------ ------ ------ DTG
Slide24HIV SCIENCE AND CARE1996-2013
US & Europe (“Resource Rich”)Fine tuning 1996-nowTreatment “done” – 2008 (Fauci)New priorities: • International • Domestic: Cure & PreventionInternational (“Low Resource”)Resource limits: DrugsInfrastructure for chronic careWHO – Plan universal ART when resources allow
Slide25President Bill ClintonState of the Union Speech: 2000
“AIDS in Africa is so devastating – it threatens the social, political and economic stability of the world” ↓ Clinton Foundation (2001) • Low cost drugs • Pediatric HIV
Slide26Subsaharan Africa:12% global population69% of HIV cases
Slide27Slide28CLINTON FOUNDATION 2002-
2002
2012
Art:
Cost/yr
$12,000
$100-200
No.
on ART
20,000
6,000,000
Slide29President George W. BushPEPFAR: 2002
Bush: Do those HIV drugs work?O’Neil: “Let me tell you about my morning in the Moore Clinic”Bush: “Tony , we need to do something, Think big – really big”
Slide30President George W. Bush
Fauci: “Thinking big”Collaborators – M. Dybul, P. Mugyeni, E. Goosby, J.W. PapePlan Proposed: Would be consideredJanuary 2003: “Seldom have we been offered the opportunity to do so much for so many”
Slide31Peter Mugyeni and Laura BushState of the Union Address
Bush: “$15 billion for Africa”Mugyeni: Jumped up → cheered → hugged the First Lady
Slide32Bono
: “PEPFAR – Greatest act of heroism since
we jumped into WWII”
NYTimes
12/1/11
Slide33Need to put banner
Prominent Voices to Address AIDS 2012Leaders from the worlds of science, diplomacy, politics, philanthropy and entertainment are speaking at AIDS 2012, including: President Bill Clinton U.S. Secretary of State Hillary Rodham Clinton U.S. Secretary of Health and Human Services Kathleen Sebelius South African Deputy President Kgalema Motlanthe Former U.S. First Lady Laura Bush HRH Mette-Marit, Crown Princess of Norway World Bank President Jim Yong Kim UNAIDS Executive Director Michel Sidibé Nobel Laureate Françoise Barré-Sinoussi NIAID Director Anthony Fauci Philanthropist Bill Gates Humanitarian Elton John Actress Whoopi Goldberg
Slide34Hillary Rodham Clinton2012 IAS Conference – Washington DC
“Blueprint for an AIDS-free generation”
Slide35HIV REVIEW
History
Current standards
Future
Slide36HIV TREATMENT (DHHS & IAS-USA)
Test: All persons age 13-64 yrs yrs(CDC); annual if riskTreat: Everybody with HIVWhat: TDF/FTC or ABC/3TC plus EFV, DRV/r, ATV/r, RALMonitor: VL, CD4, etc.Change: VL >200 or ADR
Slide37LIFE EXPECTANCY – DENMARKHelleberg M. CID 2012 [in press]
35 year old man HIV
HIVSmokesSurvivaloo78.4 yrs+o73.3 yrso+66.1 yrs++62.6 yrs
Slide38HIV CARE AND RESEARCH
1983-1996 2005-2013Care: OIs, PCP, CMV, MAC, KS, CryptoCare: CVD, Lipids, DM, HBP, Bones Neuro: Dementia, NeuropathyNeuro: DementiaPsych: DepressionPsych: VariablePatients: StigmaPatients: SameProvider: Burn-outProvider: Is it a specialty?Research: Vaccine and TreatmentResearch: Immune activa- tion, prevention
Slide39HIV REVIEW
History
Current standards
Future
Slide40HIV: THE FUTURE (US)
Research prioritiesTreatment – done (2008)PreventionCureOperational challengesCare delivery: 28% have controlled HIV viremiaWho will be primary provider (Is this a specialtyHealthcare reform
Slide41Transmission
HIV transmission efficiency correlates with Viral Load – No transmissions with VL <1500 c/mL (2000)Transmission efficiency• 1/900 coital acts• M→F & F→M near equal• Maximum risk in primary HIVTreatment for prevention• HPTN 052 (2012)• Changed Global policyNever been a confirmed case with sexual transmission (BMHIVA) (2013)
Quinn T. NEJM 2000;342:921
Slide42HIV TREATMENT FOR PREVENTION:HPTN 052 M. Cohen (PI) (Cohen MS. NEJM 2011;365:493)
Protocol: Discordant couples, CD4 350-550: Randomized to ART vs. no ART until CD4 <250Results: N=1,763 (M=890, F-873) ART No Art n=886 n=877HIV transmission* 1*** 27** *Linked cases (28 transmissions unlinked) **Protection with ART = 96% -- Study continues to determine durability***Single exception preceded viral suppression
Slide43HPTN 052:
The study that changed HIV global strategy
Slide44Treatment as Prevention: Effect of ART Coverage on HIV Incidence in Rural South Africa(Tanser F. 2012 CROI;Abstr. 136LV)
Annual population based HIV surveillance in rural KwaZulu-Natal2004 – 2011: 1395 HIV seroconversions among 16,588 HIV negative adults ≥15 years of age
Adjusted HIV Infection Rate by ARV Coverage Category
Spatial Estimates of Proportion of HIV Patients on ART
P=0.590
P=0.002
P<0.001
P=0.015
2007
2008
2009
2010
2011
<10%
10-20%
20-30%
30-40%
>40%
Tanser F, et al. 19th CROI; Seattle, WA; March 5-8, 2012. Abst. 136LB.
Slide45Efficacy of Daily OralFTC/TDF PrEP
TrialPop.Efficacy95% CIiPrExMSM42%18 to 60%Partners PrEPMen83%49 to 94%Women62%19 to 82%TDF2Men80%25 to 97%FemPrep*Women49%-22 to 81%VOICES*womenTDF only arm discontinued
Candidates: High risk MSM and discordant couples
FDA approved TDF/FTC for PrEP July 2012
.
Slide46“The Berlin Patient”
HIV + leukemia → chemotherapy and stem cell tx → 5 yrs; No HIV detected (R. Siliciano)2012: 2 more patients – Brigham Hospital, Boston (IAS Conference 2012)
Slide47The “Gardner Cascade”(Gardner EM. CID 2011;52:793)
Slide48Estimated 14% have viral suppression!!
Slide49MAKE IT EASY
Sensitivity: 93%Specificity: 99.8%Distribution: Walmart, CVS, Walgreens, RiteAid, Kroger, etc.
Slide50P4P4P: THE STATUS OF PAYING PATIENTS FOR SELF CARE
Practice: Widespread and internationalIncentives: Cash, groceries, lottery tickets, meal tickets.Conditions: Chronic – smoking, obesity , BP control, diabetes, HIVHIV trial: HPTN 65 – Controlled trial, (unblinded) HIV test – $25, Enroll in care – $70, NDV – $280/yr (1.7% of HIV care cost)Status: Widely practiced, no one wants to talk about it. Adherence guidelines refused (Ann Intern Med 2012;156:817)
Slide51A TEST OF FINANCIAL INCENTIVES TO IMPROVE WARFARIN ADHERENCE
(Volpp KG. BMC Health Sys Res 2008;8:272)
Slide52Slide53COST OF CARE
Contemporary costs/yr.(AIDS 2010;24:2705)HAART – $12,000 (72%)Meds – other – $2,100In-patient – $600Out-patient – $400 (2%)Total (Meds) – $16,600Generic 3TC/EFV +TDF: Reduce cost $6K/yr=$1B – BUT 3 pills/d(Walensky R. Ann Intern Med 2013;158:84)
Slide54HIV WITH 2013 HEALTHCARE REFORM
Slide55SUMMARY
History: GloriousFailure: Vaccine and cureChallenge: Care delivery, prevention and costFuture: Who will provide HIV care and who will payExpectation: Diabetes model